Background
REPRIEVE established that pitavastatin prevents major adverse cardiovascular events (MACE) and reduces noncalcified coronary plaque (NCP) on coronary CT angiography, in low-moderate risk PWH. We leveraged the REPRIEVE Mechanistic Substudy to assess for the first time the relationship of coronary plaque and indices of inflammation and subclinical myocardial injury with MACE and the effects of pitavastatin on MACE.
Methods
REPRIEVE Mechanistic Substudy participants (N=804) enrolled from April 2015 to February 2018 at 31 US sites, randomized to pitavastatin 4 mg/day or placebo, were followed for incident MACE over median 5.9 yrs. We assessed the relationship of baseline NCP (n=755), markers of inflammation (hs-CRP, IL-6, and LpPLA-2) (n=790), as well as markers of subclinical myocardial injury (hs-cTnT) (n=750) with MACE and the modification of the statin effect by these parameters, using Cox proportional hazards models stratified by statin randomization.
Results
Of enrolled participants (17% female, 47% non-White, median age 51 yrs, LDL 105 mg/dL, 10-year cardiovascular risk 4.6%), MACE incidence was 7.26/1000 person-years (17 events) for pitavastatin and 9.15/1000 person-years (21 events) for placebo.
40% (302/755) of participants had NCP at baseline. NCP was present in 62% (23/37) of those with MACE compared to 39% (279/718) without MACE. The risk of MACE was greater in those with NCP vs. without (HR 2.5, [CI 1.3, 4.8], P=0.008 (Figure)). Elevated levels of hs-CRP (P=0.049) and hs-cTnT (P=0.003) and higher IL-6 (P=0.033) at study entry were associated with MACE (Figure). These trends persisted after adjusting for ASCVD risk.
The effect of pitavastatin to reduce MACE was higher in those with NCP (HR 0.56 (0.24, 1.31) vs. those without 1.28 (0.44, 3.68)). Likewise, a greater effect of pitavastatin was observed in those with elevated hs-cTnT (>7.5ng/L) vs. those without (HR 0.68 (0.30, 1.53) vs. 1.66 (0.40, 6.93)). However, confidence intervals overlapped given the small number of events in the substudy.
Conclusions
NCP and higher hs-cTnT, hs-CRP, and IL-6 are associated with MACE in asymptomatic low-moderate risk PWH. This analysis suggests that the benefit of pitavastatin to prevent MACE may be greater in persons with preexisting plaque and baseline levels of subclinical myocardial injury. Further investigation is needed to determine whether plaque and/or biomarkers can help identify PWH at highest risk who would most benefit from statin prevention.